Determination of phrenic nerve stimulation threshold

ABSTRACT

In an example of a method, the method includes testing for phrenic nerve stimulation (PS) threshold. If PS beats are detected at the pacing output level, analyzing the detected PS beats using criteria to determine if the pacing output level can be declared to be the PS threshold. If the pacing output level cannot be declared to be the PS threshold based on the analysis of the PS beat at the pacing output level, performing a PS beat confirmation procedure. The PS beat confirmation procedure may include delivering additional cardiac paces at the pacing output level to generate additional PS beats, and analyzing the detected PS beats using other criteria to determine if the pacing output level can be confirmed as the PS threshold.

CLAIM OF PRIORITY

This application claims the benefit of priority under 35 U.S.C. §119(e)of Dong et al., U.S. Provisional Patent Application Ser. No. 61/616,300,entitled “DETERMINATION OF PHRENIC NERVE STIMULATION THRESHOLD”, filedon Mar. 27, 2012, which is herein incorporated by reference in itsentirety.

TECHNICAL FIELD

This application is related generally to medical devices and, moreparticularly, to cardiac pacing systems, devices and methods thataddress unintended phrenic nerve stimulation.

BACKGROUND

Implanted pacing systems may be used to deliver cardiacresynchronization therapy (CRT) or to otherwise pace the heart. When theheart is paced in the left ventricle (LV), for example, there may beunwanted stimulation of the phrenic nerve that causes contraction of thediaphragm. Unintended phrenic nerve activation (an unintended actionpotential propagated in the phrenic nerve) is a well-known consequenceof left ventricular pacing. The left phrenic nerve, for example,descends on the pericardium to penetrate the left part of the diaphragm.In most people, the left phrenic nerve runs close to the lateral vein.The unintended phrenic nerve activation may cause the diaphragm toundesirably contract. Unintended phrenic nerve activation may feel likehiccups to the patient. Such unintended phrenic nerve activation canoccur when the electric field of the LV pacing lead is proximate to theleft phrenic nerve and is at a stimulation output that is strong enoughto capture the nerve.

Unintended phrenic nerve activation may vary from patient to patient.One reason for this variance is that the anatomic location of thephrenic nerve can vary within patients. Additionally, the veins are notalways in the same location with respect to the ventricle and the nearbypassing nerve. Also, the selected vein in which to place a cardiac leadfor a prescribed cardiac therapy may vary.

Cardiac therapies may be delivered using different pacing configurationsand different stimulation parameters. Examples of pacing configurationsinclude LV bipolar, LV to can, and LV to RV (right ventricle) alsoreferred to as “extended bipolar.” Examples of stimulation parametersinclude the amplitude (e.g. voltage) and pulse width. The pacingconfiguration or the stimulation parameters of a therapy may be modifiedin an effort to avoid phrenic nerve stimulation.

For example, an implantation procedure may be modified to avoid phrenicnerve capture. For example, the LV pacing electrodes may be repositionedto capture the LV for a pacing therapy such as CRT while avoidingphrenic nerve capture, or the clinician may decide not to implant an LVpacing electrode but rather rely on other pacing algorithms that do notpace the LV.

Although phrenic nerve stimulation is commonly assessed at implant,unintended phrenic nerve activation caused by phrenic nerve captureduring pacing may first appear or worsen post-implant for a variety ofreasons such as reverse remodeling of the heart, leadmicro-dislodgement, changes in posture, and the like. Therefore, specialoffice visits after implant may be necessary or desirable to reprogramthe device to avoid phrenic nerve stimulation.

SUMMARY

In an example of a method, the method includes testing for phrenic nervestimulation (PS) threshold. If PS beats are detected at the pacingoutput level, the detected PS beats may be analyzed using criteria todetermine if the pacing output level can be declared to be the PSthreshold. If the pacing output level cannot be declared to be the PSthreshold based on the analysis of the PS beat at the pacing outputlevel, performing a PS beat confirmation procedure. The PS beatconfirmation procedure may include delivering additional cardiac pacesat the pacing output level to generate additional PS beats, andanalyzing the detected PS beats using other criteria to determine if thepacing output level can be confirmed as the PS threshold.

In an example, a system includes a cardiac pulse generator configured togenerate cardiac paces to pace the heart, a sensor configured to sense aphysiological signal for use in detecting pace-induced phrenic nervestimulation, a phrenic nerve stimulation detector configured to analyzethe sensed physiological signal to detect PS beats, and a controllerconfigured to test for phrenic nerve stimulation (PS) threshold. Thecontroller may be configured to control the cardiac pulse generator todeliver cardiac paces at a pacing output level, use the phrenic nervestimulation detector to detect if the pacing output level causes PSbeats, analyze the detected PS beats, if PS beats are detected at thepacing output level, using criteria to determine if the pacing outputlevel can be declared to be the PS threshold, and perform a PS beatconfirmation procedure, if the pacing output level cannot be declared tobe the PS threshold based on the analysis of the PS beat at the pacingoutput level. The PS beat confirmation procedure may include deliveringadditional cardiac paces at the pacing output level to generateadditional PS beats, and analyzing the detected PS beats using othercriteria to determine if the pacing output level can be confirmed as thePS threshold. The system may include at least one implantable medicaldevice that includes the cardiac pulse generator, the sensor, thephrenic nerve stimulation detector and the controller. The system mayinclude at least one implantable medical device and at least oneexternal device, where the implantable medical device(s) include thecardiac pulse generator, and the external device(s) include the phrenicnerve stimulation detector.

This Summary is an overview of some of the teachings of the presentapplication and is not intended to be an exclusive or exhaustivetreatment of the present subject matter. Further details about thepresent subject matter are found in the detailed description andappended claims. The scope of the present invention is defined by theappended claims and their equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments are illustrated by way of example in the figures ofthe accompanying drawings. Such embodiments are demonstrative and notintended to be exhaustive or exclusive embodiments of the presentsubject matter.

FIG. 1 illustrates, by way of example, an embodiment of an implantablemedical device (IMD) configured to deliver myocardial stimulation.

FIG. 2 illustrates, by way of example, an embodiment of an IMD.

FIG. 3 illustrates, by way of example, an embodiment of a system thatincludes two or more IMDs.

FIG. 4 illustrates, by way of example, an embodiment of a system thatincludes an IMD, an external device, and an external phrenic nervestimulation (PS) sensor.

FIG. 5 illustrates, by way of example, a system diagram of an embodimentof a microprocessor-based implantable device.

FIG. 6 is a block diagram illustrating, by way of example, an embodimentof an external system.

FIG. 7 illustrates, by way of example, sensor-based signals that may beused by a PS detector.

FIG. 8 illustrates, for example, an embodiment of a procedure todetermine a baseline level of the sensor-based signal.

FIG. 9 illustrates, for example, an embodiment of a procedure for addingsamples from new beats for a moving window used to determine a baselinelevel of the sensor-based signal.

FIG. 10 illustrates, for example, an embodiment of a procedure for usingthe baseline level to discriminate between PS beats and NoPS beats.

FIG. 11 is a plot of the peak-to-peak amplitude of sampled beats, whichillustrates, by way of example, how the baseline peak-to-peak amplitudecan be used to discriminate between NoPS beats whose peak-to-peakamplitudes are close to the baseline levels, and PS beats whosepeak-to-peak amplitudes are significantly larger than the baselinelevels.

FIG. 12 illustrates, by way of example, an embodiment of a procedure fordeveloping a library of PS templates that may be used to discriminatebetween PS beats and NoPS beats.

FIG. 13 illustrates, by way of example, an embodiment of a procedure forusing PS templates to discriminate between PS beats and NoPS beats.

FIG. 14 illustrates a plot of beat signals against beat-type categories,and a corresponding histogram that plots out a number of beat-typecategories and the number of beats that have been tallied in thatcategory.

FIG. 15 illustrates, by way of example, an embodiment of a procedure forusing morphological features of a sensor-based signal to discriminatebetween PS beats and NoPS beats.

FIGS. 16A-16G illustrate, by way of example, an embodiment of aprocedure for using signal peaks, as a morphological feature for asensor-based signal, to discriminate between PS beats and NoPS beats.

FIG. 17 illustrates, by way of example, an embodiment of a procedure forscoring sensed parameters for specific morphological features.

FIG. 18 illustrates, by way of example, an embodiment of a procedure forusing a decision tree for analyzing morphological features of the beatsignal to discriminate between PS beats and no PS beats.

FIG. 19 illustrates, by way of example, an embodiment of a procedure fordiscriminating PS beats using both a decision tree for analyzingmorphological features of the beat signal and scoring sensed parametersfor specific morphological features.

FIG. 20 illustrates, by way of example, an embodiment of a procedure fordiscriminating PS beats that uses correlation to create templates in alibrary and to score the beat signals to quickly identify the beat-typetemplates that can be labeled as a PS template.

FIG. 21 illustrates, by way of example, an embodiment of a procedure fordiscriminating PS beats that scores morphological features of the beatsignals to quickly identify some beat signals as PS beats or NoPS beats,and that correlates the remainder of the beat signals to a PS templateto discriminate between PS beats and NoPS beats.

FIG. 22 illustrates, by way of example, an embodiment of a step-upprocedure for determining a PS threshold.

FIG. 23 illustrates, by way of example, an embodiment of a procedure forconfirming a PS threshold by increasing the pacing output level.

FIG. 24 illustrates, by way of example, an embodiment of a procedure forconfirming a PS threshold by reducing the pacing output level.

FIG. 25 illustrates, by way of example, an embodiment of a step-downprocedure for determining a PS threshold.

DETAILED DESCRIPTION

The following detailed description of the present subject matter refersto the accompanying drawings which show, by way of illustration,specific aspects and embodiments in which the present subject matter maybe practiced. These embodiments are described in sufficient detail toenable those skilled in the art to practice the present subject matter.Other embodiments may be utilized and structural, logical, andelectrical changes may be made without departing from the scope of thepresent subject matter. References to “an,” “one,” or “various”embodiments in this disclosure are not necessarily to the sameembodiment, and such references contemplate more than one embodiment.The following detailed description is, therefore, not to be taken in alimiting sense, and the scope is defined only by the appended claims,along with the full scope of legal equivalents to which such claims areentitled.

Some embodiments, for example, implement an automatic detectionalgorithm for detecting unintended phrenic nerve activation (alsoreferred to herein as pace-induced phrenic nerve stimulation or asphrenic nerve stimulation “PS”). According to various embodiments, thePS detection algorithm can be used in a clinical setting such as duringimplant procedures or in patient follow-up visits, or an ambulatorysetting such as in a patient's home, or in both the clinical andambulatory setting. The PS detection algorithm may lessen or alleviatethe burden of the patients and clinical staff to adequately address theproblems of unintended PS that may occur during myocardial stimulation.For example, the ability to accurately and/or automatically detect PSmay reduce prolonged discomfort for patients experiencing PS, and mayreduce the burden on hospitals and staff for testing and reprogrammingdevices.

The PS algorithm is capable of addressing problems with automaticallydetecting PS. Even when a patient is sitting quietly, it can bedifficult to sense signals close to the PS threshold. For example, itcan be difficult to process low-peak-to-peak amplitudes of sensed PSresponses from the deflection variations observed in the accelerometeror other PS sensor, especially those close to the PS threshold. It canalso be difficult to detect PS because different patients have PSresponse of various amplitudes.

Myocardial Stimulation

A myocardial stimulation therapy may deliver a cardiac therapy usingelectrical stimulation of the myocardium. Some examples of myocardialstimulation therapies, and devices for performing the therapies, areprovided below. A pacemaker is a device which paces the heart with timedpacing pulses, most commonly for the treatment of bradycardia where theventricular rate is too slow. If functioning properly, the pacemakermakes up for the heart's inability to pace itself at an appropriaterhythm in order to meet metabolic demand by enforcing a minimum heartrate. Implantable devices have also been developed that affect themanner and degree to which the heart chambers contract during a cardiaccycle in order to promote the efficient pumping of blood. The heartpumps more effectively when the chambers contract in a coordinatedmanner, a result normally provided by the specialized conductionpathways in both the atria and the ventricles that enable the rapidconduction of excitation (i.e., depolarization) throughout themyocardium. These pathways conduct excitatory impulses from the sinθ-atrial node to the atrial myocardium, to the atrio-ventricular node,and then to the ventricular myocardium to provide a coordinatedcontraction of both atria and both ventricles. This both synchronizesthe contractions of the muscle fibers of each chamber and synchronizesthe contraction of each atrium or ventricle with the contralateralatrium or ventricle. Without the synchronization afforded by thenormally functioning specialized conduction pathways, the heart'spumping efficiency is greatly diminished. Pathology of these conductionpathways and other inter-ventricular or intra-ventricular conductiondeficits can be a causative factor in heart failure. Heart failurerefers to a clinical syndrome in which an abnormality of cardiacfunction causes cardiac output to fall below a level adequate to meetthe metabolic demand of peripheral tissues. In order to treat theseproblems, implantable cardiac devices have been developed that provideappropriately timed electrical stimulation to one or more heart chambersin an attempt to improve the coordination of atrial and/or ventricularcontractions, termed cardiac resynchronization therapy (CRT).Ventricular resynchronization is useful in treating heart failurebecause, although not directly inotropic, resynchronization can resultin a more coordinated contraction of the ventricles with improvedpumping efficiency and increased cardiac output. A CRT example appliesstimulation pulses to both ventricles, either simultaneously orseparated by a specified biventricular offset interval, and after aspecified atrio-ventricular delay interval with respect to the detectionof an intrinsic atrial contraction or delivery of an atrial pace.

CRT can be beneficial in reducing the deleterious ventricular remodelingwhich can occur in post-myocardial infarction (MI) and heart failurepatients, which appears to occur as a result of changes in thedistribution of wall stress experienced by the ventricles during thecardiac pumping cycle when CRT is applied. The degree to which a heartmuscle fiber is stretched before it contracts is termed the preload, andthe maximum tension and velocity of shortening of a muscle fiberincreases with increasing preload. When a myocardial region contractslate relative to other regions, the contraction of those opposingregions stretches the later contracting region and increases thepreload. The degree of tension or stress on a heart muscle fiber as itcontracts is termed the afterload. Because pressure within theventricles rises rapidly from a diastolic to a systolic value as bloodis pumped out into the aorta and pulmonary arteries, the part of theventricle that first contracts due to an excitatory stimulation pulsedoes so against a lower afterload than does a part of the ventriclecontracting later. Thus a myocardial region which contracts later thanother regions is subjected to both an increased preload and afterload.This situation is created frequently by the ventricular conductiondelays associated with heart failure and ventricular dysfunction due toan MI. The increased wall stress to the late-activating myocardialregions may be the trigger for ventricular remodeling. Pacing one ormore sites may cause a more coordinated contraction, by providingpre-excitation of myocardial regions which would otherwise be activatedlater during systole and experience increased wall stress. Thepre-excitation of the remodeled region relative to other regions unloadsthe region from mechanical stress and allows reversal or prevention ofremodeling to occur.

Cardioversion, an electrical shock delivered to the heart synchronouslywith the QRS complex, and defibrillation, an electrical shock deliveredwithout synchronization to the QRS complex, can be used to terminatemost tachyarrhythmias. The electric shock terminates the tachyarrhythmiaby simultaneously depolarizing the myocardium and rendering itrefractory. A class of CRM devices known as an implantable cardioverterdefibrillator (ICD) provides this kind of therapy by delivering a shockpulse to the heart when the device detects tachyarrhythmias. Anothertype of electrical therapy for tachycardia is anti-tachycardia pacing(ATP). In ventricular ATP, the ventricles are competitively paced withone or more pacing pulses in an effort to interrupt the reentrantcircuit causing the tachycardia. Modern ICDs typically have ATPcapability, and deliver ATP therapy or a shock pulse when atachyarrhythmia is detected. ATP may be referred to as overdrive pacing.Other overdrive pacing therapies exist, such as intermittent pacingtherapy (IPT), which may also be referred to as a conditioning therapy.

Phrenic Nerves

Both a right phrenic nerve and a left phrenic nerve pass near the heartand innervate the diaphragm below the heart. Pace-induced phrenic nerveactivation, also referred to herein as PS, may be observed with variousforms of pacing. PS may be observed particularly with LV pacing becauseof the close proximity of the LV pacing site to the left phrenic nerve.PS is a common side effect of CRT. Cardiac stimulation at otherlocations of the heart may result in PS in either the left or rightphrenic nerve. The present subject matter is not limited to PS of theleft phrenic nerve during LV pacing, but may be implemented toappropriately address PS in either the left or right phrenic nervecaused by myocardial stimulation.

PS may be observed only when a patient is in a particular position (e.g.lying down) or activity level. The unintended phrenic nerve activationmay not have been observed at the time that the stimulation device wasimplanted because of the patient position at the time of implantation,because of the effects of anesthesia, or because of other factors thatare not present in a clinical setting. Some embodiments use a posturesensor to provide context. Some embodiments use an activity sensor toprovide context. Some embodiments use a timer to determine a time of dayto provide context. Some embodiments allow the device to store posture,activity, time of day and the like with the detected PS data todetermine the context when the PS is observed.

FIG. 1 illustrates, by way of example, an embodiment of an implantablemedical device (IMD) configured to deliver myocardial stimulation. Theillustrated IMD 100 is used to perform a cardiac tissue stimulationtherapy, such as CRT or other pacing therapies, using leads representedby the dotted lines and electrodes represented by “X” fed into the rightatrium, right ventricle, and coronary sinus of the heart. The lead 101passing through the coronary sinus of the heart includes a leftventricular electrode 102, or electrodes, for use to stimulate the leftventricle at a stimulation site. FIG. 1 also indicates that the leftventricular electrode 102 of the lead 101 is relatively close to theleft phrenic nerve 103. PS may occur for certain configurations ofpacing vectors or electrode placement. Various embodiments of thepresent subject matter may be used in processes for using PS sensor(s)to detect PS. A PS sensor is a sensor that may be used to detectunintended phrenic nerve activity. By way of example and not limitation,a PS sensor may include a sensor to detect motion caused by thediaphragm induced by PS. For example, some embodiments use anaccelerometer to detect PS. Other examples of sensors that may be usedto detect PS include, but are not limited to, an acoustic sensor, arespiration sensor, an impedance sensor, a neural sensor on the phrenicnerve, or an electromyogram (EMG) sensor for sensing signals indicativeof diaphragm contraction.

FIG. 2 illustrates an embodiment of an implantable medical device (IMD).The illustrated IMD 204 may be used to deliver myocardial stimulation,and to detect PS unintentionally caused by the myocardial stimulation.The illustrated IMD 204 includes a controller 205, a cardiac pacegenerator 206, a PS sensor 207, and a cardiac activity sensor 208. Insome embodiments, the IMD 204 may also include one or more other sensorssuch as, by way of example and not limitation, a sensor used fordetecting posture, a sensor used for detecting respiration or arespiration cycle, or a sensor used for detecting activity. In someembodiments, the device implements a cardiac pacing algorithm, in whichthe controller 205 receives sensed cardiac activity from the cardiacactivity sensor 208, uses timer(s) 209, such as a cardiac pacing timer,to determine a pace time for delivering a cardiac pace or othermyocardial stimulation pulse, and controls the cardiac pace generator206 to deliver the cardiac pace at the desired time. The controller 205also includes a PS detector 210 that cooperates with the PS sensor 207to discriminate if a signal from the PS sensor 207 is indicative of PSevents.

In some embodiments, the IMD 204 may be configured with a PS thresholdtest module 211 used to perform PS threshold test(s). The PS thresholdtest may be configured to deliver myocardial stimulation using differentstimulation parameters. The PS threshold tests may be configured todetermine the myocardial stimulation parameters that cause or that maycause PS, or myocardial stimulation parameters that do not cause PS. Thephysical position of the stimulation electrode or electrodes used todeliver the myocardial stimulation may be adjusted in an attempt toavoid PS, such as may occur during an implantation procedure. Aphysician may physically move the electrode. Some embodiments mayprovide electronic repositioning by selecting a set of stimulationelectrodes from a larger set of potential stimulation electrodes. Insome embodiments, the pacing vector between or among stimulationelectrodes may be modified in an attempt to avoid PS. The controller insome IMD embodiments may include a pacing vector control module 212 usedto change the pacing vectors. The pacing vector control may beimplemented under the control of a clinician through an externalprogrammer, or may be implemented autonomously by the IMD such as mayoccur in an ambulatory setting.

The PS detection may occur in the same IMD that is providing themyocardial stimulation, or may occur in another IMD. Thus, for example,an accelerometer used to provide the PS detection may be positioned nearthe diaphragm or near the portion of the diaphragm innervated by thephrenic nerve or near the apex of the heart, which may improve thesignal to noise characteristics of the sensed signal. FIG. 3 illustratesan embodiment of a system that includes two or more IMDs. A first one ofthe IMDs 313 in the illustrated system includes a cardiac stimulatorconfigured to deliver myocardial stimulation pulses. By way of exampleand not limitation, the first IMD may be a pacemaker or other cardiacrhythm management device. A second one of the IMDs 314 in theillustrated system includes a PS detector/sensor used to detect PS thatmay be caused by the myocardial stimulation pulses delivered from thefirst one of the IMDs. In some embodiments, the IMDs 313, 314 maycommunicate with each other over a wired connection. In someembodiments, the IMDs 313, 314 may communicate with each otherwirelessly using ultrasound or radiofrequency (RF) or other wirelesstechnology.

The sensor(s) used for detecting PS may be implanted or may be external.The algorithms for processing the sensed signals to detect PS may beperformed within the IMD(s) and/or may be performed in external devices.By way of example, some embodiments may use implantable sensor(s) anduse external device(s) to process the sensed signals to detect PS. Themonitoring of the patient for PS may be performed in a clinical settingor in an ambulatory setting. This monitoring, regardless of whether itis performed in the clinical setting or an ambulatory setting, may beperformed using implanted PS detectors such as illustrated in FIGS. 2-3,for example, and/or may be performed using external PS detectors.

FIG. 4 illustrates an embodiment of a system that includes an IMD 415,such as a cardiac rhythm management device, an external device 416 suchas a programmer, and an external PS sensor 417. The system may beimplemented in a clinical setting, such as by a clinician who uses aprogrammer to program the IMD, or may be implemented by the patient inan ambulatory setting to occasionally check if the myocardialstimulation is causing PS. In various embodiments, the external deviceincludes a PS detector that cooperates with the PS sensor todiscriminate if a signal from the PS sensor indicates the presence of PSevents. In various embodiments, the external device includes a PSthreshold test module used to perform PS threshold test(s). The PSthreshold test may be configured to control the IMD to delivermyocardial stimulation using different stimulation parameters. The PSthreshold tests may be configured to determine the myocardialstimulation parameters that cause or that may cause PS, or myocardialstimulation parameters that do not cause PS. The physical position ofthe stimulation electrode or electrodes used to deliver the myocardialstimulation may be adjusted in an attempt to avoid PS, such as may occurduring an implantation procedure. In some embodiments, the pacing vectorbetween or among stimulation electrodes may be modified in an attempt toavoid PS. In some embodiments, the external PS sensor 417 may beintegrated with the external device 416, such that the PS may be sensedby holding or otherwise positioning the external device next to thepatient (e.g. externally positioned near the diaphragm or near the apexof the heart).

FIG. 5 illustrates a system diagram of an embodiment of amicroprocessor-based implantable device. The controller of the device isa microprocessor 518 which communicates with a memory 519 via abidirectional data bus. The controller could be implemented by othertypes of logic circuitry (e.g., discrete components or programmablelogic arrays) using a state machine type of design. As used herein, theterm “circuitry” should be taken to refer to either discrete logiccircuitry, firmware, or to the programming of a microprocessor. Shown inthe figure are three examples of sensing and pacing channels comprisingleads with ring electrodes 520 and tip electrodes 521, sensingamplifiers 522, pulse generators 523, and channel interfaces 524. One ofthe illustrated leads includes multiple ring electrodes 520, such as maybe used in a multi-polar lead. An example of a multipolar lead is a leftventricle quadripolar lead. In some embodiments, the leads of thecardiac stimulation electrodes are replaced by wireless links. Eachchannel thus includes a pacing channel made up of the pulse generatorconnected to the electrode and a sensing channel made up of the senseamplifier connected to the electrode. The channel interfaces communicatebidirectionally with the microprocessor, and each interface may includeanalog-to-digital converters for digitizing sensing signal inputs fromthe sensing amplifiers and registers that can be written to by themicroprocessor in order to output pacing pulses, change the pacing pulseamplitude, and adjust the gain and threshold values for the sensingamplifiers. The sensing circuitry of the pacemaker detects intrinsicchamber activity, termed either an atrial sense or ventricular sense,when an electrogram signal (i.e., a voltage sensed by an electroderepresenting cardiac electrical activity) generated by a particularchannel exceeds a specified detection threshold. Pacing algorithms usedin particular pacing modes employ such senses to trigger or inhibitpacing. The intrinsic atrial and/or ventricular rates can be measured bymeasuring the time intervals between atrial and ventricular senses,respectively, and used to detect atrial and ventriculartachyarrhythmias.

The electrodes of each lead are connected via conductors within the leadto a switching network 525 controlled by the microprocessor. Theswitching network is used to switch the electrodes to the input of asense amplifier in order to detect intrinsic cardiac activity and to theoutput of a pulse generator in order to deliver a pacing pulse. Theswitching network also enables the device to sense or pace either in abipolar mode using both the ring and tip electrodes of a lead or inunipolar or an extended bipolar mode using only one of the electrodes ofthe lead with the device housing (can) 526 or an electrode on anotherlead serving as a ground electrode. In some embodiments, a shock pulsegenerator 527 maybe interfaced to the controller, in addition oralternative to other stimulation channels, for delivering adefibrillation shock via a pair of shock electrodes 528 and 528 to theatria or ventricles upon detection of a shockable tachyarrhythmia. A canelectrode may be used to deliver shocks. The figure illustrates atelemetry interface 529 connected to the microprocessor, which can beused to communicate with an external device. As illustrated in FIG. 5,the system may include a PS sensor/detector 530 used to detectunintended phrenic nerve activations caused by myocardial stimulation.Various embodiments may also include a respiration detector 531 and/orother sensor(s) 532 such as may be used to provide contextualinformation like activity and posture. According to various embodiments,the phrenic nerve activity detector may include, but is not limited to,an accelerometer, an acoustic sensor, a respiration sensor, impedancesensors, neural sensor on the phrenic nerve, or electrodes to senseelectromyogram signals indicative of diaphragm contraction. Variousembodiments use more than one detector to provide a composite signalthat indicates phrenic nerve capture. The use of more than one detectormay enhance the confidence in detecting PS events. The illustratedembodiment also includes a clock 533.

According to various embodiments, the illustrated microprocessor 518 maybe configured to perform various cardiac tissue (e.g. myocardial)stimulation routines 534. Examples of myocardial therapy routinesinclude bradycardia pacing therapies, anti-tachycardia shock therapiessuch as cardioversion or defibrillation therapies, anti-tachycardiapacing therapies (ATP), and cardiac resynchronization therapies (CRT).As illustrated, the controller 518 may also includes a comparator 535 tocompare time when phrenic nerve activity is detected to a pace time todetermine that phrenic nerve activity is attributed to the pace, and/ormay includes a comparator 536 to compare respiration features to thepace time for use in detecting PS. The illustrated microprocessor 518may include instructions for performing a PS threshold test 511 and apacing vector control process 512, similar to the controller 205illustrated in FIG. 2

FIG. 6 is a block diagram illustrating an embodiment of an externalsystem 637. For example, the system may be used to remotely program theimplanted device in an ambulatory patient, or to remotely obtaindetected PS events from an ambulatory patient, or to remotely retrievesensed data from the implanted device in an ambulatory patient foranalysis of the sensed data for the PS event in a remote location fromthe ambulatory patient. The external system includes a programmer, insome embodiments. In the illustrated embodiment, the external systemincludes a patient management system. As illustrated, the externalsystem is a patient management system including an external device 638,a telecommunication network 639, and a remote device 640 removed fromthe external device 638. The external device 638 is placed within thevicinity of an implantable medical device (IMD) 641 and includes anexternal telemetry system 642 to communicate with the IMD 641. Theremote device(s) is in one or more remote locations and communicateswith the external device through the network, thus allowing a physicianor other caregiver to monitor and treat a patient from a distantlocation and/or allowing access to various treatment resources from theone or more remote locations. The illustrated remote device includes auser interface 643. According to various embodiments, the externaldevice includes a programmer or other device such as a computer, apersonal data assistant or phone. The external device, in variousembodiments, includes two devices adapted to communicate with each otherover an appropriate communication channel, such as a computer by way ofexample and not limitation. The external device can be used by thepatient or physician to provide feedback indicative of patientdiscomfort, for example.

According to various embodiments, various processes may be implementedusing hardware, firmware, and/or software within the devices and systemsdiscussed above for use in PS detection and determining PS threshold.These processes may be, but do not have to be, integrated within thesame system. This document is organized to discuss some processes forbaseline level determination, for PS detection, and for PS stimulationthreshold determination.

Baseline Level Determination for PS Detection

Various embodiments may provide for a baseline level determination,which may be used to improve subsequent PS detection. An estimate forthe baseline level of a sensor-based signal used in the PS detection maybe used to perform Signal-to-Noise Ratio (SNR) calculations and todiscriminate between NoPS (paced heart beats without PS) and PS beats(paced heart beats with PS). Some embodiments of the present subjectmatter may be configured to dynamically determine a baseline level ofsensor-based signals used to detect PS, allowing the PS detector toautomatically and accurately identify PS in the raw signal from the PSsensor. The dynamic determination of the baseline level improves thedevice's ability to automatically differentiate PS events from otherevents in the sensor signal by accommodating patient-specificdifferences in the sensed signal, and/or by accommodatingcontext-specific differences in the sensed signal.

For example, although accelerometer-based PS sensor signals can vary inmagnitude with pacing voltage, they demonstrate similar morphologicalfeatures with different pulse widths, across different pacingconfigurations, across various postures over time and across patients.However, the PS detection should be adjusted appropriately in thepresence of interference. For example, an accelerometer-based PSdetector should accommodate baseline changes attributed to patientmovement that can be detected by the accelerometer. PS detectors basedon technology other than accelerometers also would benefit if thebaseline was periodically adjusted to accommodate environmental orcontextual changes that may be reflected as noise in the PS detector.For example, a respiration-based PS detector may have the baselineperiodically adjusted to accommodate changes in the patient's activityor health. In another example, an accelerometer-based PS detector mayhave the baseline periodically adjusted to accommodate for patientactivity, for patient environment (e.g. stationary or travel-inducedvibrations), or for patient talking or other vocalization.

FIG. 7 illustrates sensor-based signals that may be used by a PSdetector. The baseline level characteristics may be determined usingsignals collected from a baseline detection window 744 that isassociated with a pace time (e.g. time of LV pace) 745 but that does notcontain cardiac or PS components caused by the beat. For example, thebaseline detection window may start at 746 prior to the pace timing andend at 747 before any cardiac component from the pace is expected andbefore a time that one would expect a PS component, if any, to occurafter the pace. If the baseline detection window is associated with asensed beat, the window may be triggered off of, by way of example, an Rwave. The start and/or end times for the baseline detection window maybe appropriately adjusted, depending on whether the detection window istriggered off of a sensed beat (e.g. sensed R wave) or triggered off ofthe pace. By way of example and not limitation, the baseline window mayoccur approximately 100 ms before a pace and extend 10 ms after thepace, where an accelerometer-based PS detector may be expected to detecta cardiac component more than 10 ms after the pace, and where the PS isalso expected to occur, if at all, more than 10 ms after the pace. Thebaseline noise range 748 can be determined from the signal within thisbaseline detection window 744.

FIG. 8 illustrates, for example, an embodiment of a procedure todetermine a baseline level of the sensor-based signal. During aninitialization period 849, information from several beats is gathered inorder to calculate an initial baseline level. About 20 beats may beaveraged during the initialization period, by way of example and notlimitation. In the illustrated procedure, sampled signal data fromwithin the baseline detection window are stored in a queue for the firstN cardiac cycles 850, and the maximum peak-to-peak amplitude of thesignals is determined 851.

The baseline level characteristics can be updated with each new beatusing a moving window. The characteristics of the baseline level may becompared to the beat characteristics in order to help differentiatebetween cardiac beats that cause PS (“PS beats”) and cardiac beats thatdo not cause PS (“NoPS beats”). For example, a moving window of 20 beatsmay be used to determine an updated baseline level. In the illustratedprocedure, sampled signal data from the baseline detection window isstored for a subsequent cardiac cycle 852, and the peak-to-peakamplitude is determined for the new sample 853.

In some embodiments, a beat is only included in the moving window if itsatisfies certain criteria that indicates that it has a minimal level ofnoise that is not reflective of the baseline level. A beat amplitude maybe required to fall within a peak-to-peak value. For example, thefollowing equation may be used to define an acceptable peak-to-peakvalue for the beat: baseline levelpeak-to-peak=max((mean+2*SD)−(mean−2*SD)), where the mean and standarddeviation (SD) are taken of all the valid samples in the queue for eachtime point. Various embodiments may provide a procedure to dynamicallyadjust the baseline level and to correct for baseline wandering whileremoving outlier beats which may not accurately reflect the change inthe baseline level. In the illustrated procedure, a process to identifynoisy beats as outlier beats to be removed may be implemented at 854.For example, a ratio of the peak-to-peak amplitude of the beat to thequeue's peak-to-peak amplitude, which is reflective of the movingwindow, may be determined and compared to a noise ratio at 855. If theratio is greater than a noise ratio, the beat is classified as a noisybeat 856, which should be ignored in determining the baseline level.

A baseline level determination procedure can be used as a standalonefeature or in conjunction with a test for PS threshold or presence. Forexample, a baseline determination procedure can be implemented intest(s) that detect the presence of PS, and a baseline determinationprocedure can be implemented in test(s) that detect a PS threshold (e.g.a lowest pacing voltage for a pacing vector that is a PS beat). Sincethe baseline detection window is defined for a time period withoutcardiac components or PS components, it can be determined irrespectiveof the presence or absence of PS in the subsequent beat(s).

Various embodiments use context information to determine when to performa baseline level determination process to dynamically adjust thebaseline level. For example, contextual sensor, such as an activity orposture sensor, may be used to trigger the baseline level determinationprocess. Some embodiments may trigger a baseline level determinationprocess according to a schedule, which may be a programmed schedule toperiodically or intermittently trigger the process. Some embodiments maytrigger a baseline determination process based on a command receivedfrom a patient or clinician.

Some embodiments include attack and/or decay features to adjust thesensitivity to interference or noise. The attack and/or decay featuresmay be programmable. Attack and Decay are features implemented withautomatic gain control (AGC) systems. AGC systems are adaptive systemswhere the output level is used to appropriately adjust the gain forinput signal levels. The attack and decay settings determine how fastthe system responds to a changing signal input level. Attack indicateshow quickly the gain is adjusted when the input level moves away from“normal,” and decay indicates how quickly the gain returns back when theinput signal returns toward “normal.” Thus, the attack and decaysettings determine how quickly the device responds to changes, includingnoise, in the input signal.

FIG. 9 illustrates, for example, an embodiment of a procedure for addingsamples from new beats for a moving window used to determine a baselinelevel of the sensor-based signal. Some embodiments may correct for abaseline offset if the beat samples are outside of upper or lower bounds957. For example, a beat sample may be compared to the upper and lowerbounds of the queue at 958. If the beat sample lies outside of thebounds, then the procedure may adjust the beat sample at 959 so that itlies within the upper and lower bounds of the queue before the beatsample is used by the procedure to dynamically adjust the baselinelevel.

Some embodiments may remove outlier data points from being used in themoving window to determine the baseline level 960. If a data point isdetermined to be a statistical outlier from the data points in the queue961, then the outlier data point can be removed from being used in theprocedure to dynamically adjust the baseline level 962. At 963, the newbeat sample(s) is added to the queue, and the oldest beat sample(s) isremoved from the queue. The statistics of the updated queue arecalculated at 964. This may involve accumulating an ensemble of averagesand standard deviations. The baseline level characteristics arecalculated at 965. This may involve determining the peak-to-peakamplitude and the upper and lower bounds of the baseline level signal.

FIG. 10 illustrates, for example, an embodiment of a procedure for usingthe baseline level to discriminate between PS beats and NoPS beats. At1066, the baseline noise characteristics can be determined usingprocedures described above. A beat signal, which may or may not havecaused a PS during a specified window of time, is analyzed to measurecharacteristics of the signal during the specified window 1067. Thiswindow of time for the beat signal is a different timing window than thewindow used to determine the baseline level, although they may overlap.This window of time for the beat signal typically spans a time after thepace which would include PS information if PS is present. At 1068, thecharacteristics of the beat signal are compared to the baseline levelsignal. The beat is classified as a PS beat 1069 if the characteristicsof the beat signal differ significantly from the baseline signal, and isclassified as a NoPS beat 1070 if the characteristics of the beat signaldo not differ significantly from the baseline signal. For example, thepeak-to-peak amplitude of the beat signal can be compared to thepeak-to-peak amplitude of the baseline level to determine if there is alarge enough difference to identify the beat signal as a PS beat. FIG.11 is a plot of the peak-to-peak amplitude of sampled beats, whichillustrates how the baseline peak-to-peak amplitude can be used todiscriminate between NoPS beats whose peak-to-peak amplitudes are closeto the baseline levels, and PS beats whose peak-to-peak amplitudes aresignificantly larger than the baseline levels.

This procedure may be implemented for ambulatory or in-clinic use. Itmay be implemented in a standalone PS detector, or in conjunction with aPS threshold test. The PS threshold test may be implemented alone as astandalone step-up and/or step-down test, or may be implemented inconjunction with a pacing threshold test (e.g. LV threshold) such thatboth the pacing threshold and the PS threshold are determined during thesame test procedure.

In an example of a method for analyzing a sensed physiological signal todetect pace-induced phrenic nerve stimulation, the method may includesampling the sensed physiological signal during each of a plurality ofcardiac cycles to provide sampled signals, calculating a baseline levelfor the physiological signal using the sampled signals, and detectingpace-induced phrenic nerve stimulation using the sensed physiologicalsignal and the calculated baseline level. Sampling the sensedphysiological signal may include sampling the signal during a timewindow defined using a pace time or using a sensed intrinsic beat (e.g.RV timing and LV offset) with each of the cardiac cycles to avoidcardiac components and phrenic nerve stimulation components in thesampled signal. Calculating the baseline level may include using thesampled signals stored in a queue to calculate the baseline level. Thesensed physiological signal may be sampled during subsequent cardiaccycles to provide subsequent sampled signals, and the baseline level maybe dynamically adjusted for the physiological signal using thesubsequent sampled signals. Detecting pace-induced phrenic nervestimulation using the sensed physiological signal and the calculatedbaseline level may include monitoring a beat signal within the sensedphysiological signal where the beat signal is within a defined window oftime that is defined using the pace time, identifying characteristics ofthe beat signal, comparing the characteristics of the beat signal to thebaseline, and determining if the beat signal is a PS beat or a NoPS beatbased on the comparison. PS beats are determined to include apace-induced phrenic nerve stimulation response and NoPS beats aredetermined to not include the pace-induced phrenic nerve stimulationresponse. A baseline level determination process may be triggeredaccording to a schedule or a sensed context or a patient-initiated orclinician-initiated command. The baseline level determination processmay include sampling the signal during a time window defined using apace time with each of the cardiac cycles to avoid cardiac componentsand phrenic nerve stimulation components in the sampled signal, andcalculating a baseline level for the physiological signal using thesampled signals.

Some method examples may include pacing a heart with cardiac paces,sensing a physiological signal for use in detecting pace-induced phrenicnerve stimulation, performing a baseline level determination process toidentify a baseline level for the sensed physiological signal, anddetecting pace-induced phrenic nerve stimulation using the sensedphysiological signal and the calculated baseline level. Detectingpace-induced phrenic nerve stimulation may include sampling the sensedphysiological signal during each of a plurality of cardiac cycles toprovide sampled signals and calculating the baseline level for thephysiological signal using the sampled signals. Sampling the sensedphysiological signal may include sampling the signal during a timewindow defined using a pace time with each of the cardiac cycles toavoid cardiac components and phrenic nerve stimulation components in thesampled signal.

In an example of a phrenic nerve stimulation detector configured toanalyze a sensed physiological signal to detect a pace-induced phrenicnerve stimulation, the phrenic nerve stimulation detector may beconfigured to sample the sensed physiological signal during each of aplurality of cardiac cycles to provide sampled signals, calculate abaseline level for the physiological signal using the sampled signals,and detect pace-induced phrenic nerve stimulation using the sensedphysiological signal and the calculated baseline level. The signal maybe sampled during a time window defined using a pace time with each ofthe cardiac cycles to avoid cardiac components and phrenic nervestimulation components in the sampled signal. The phrenic nervestimulation detector may include a memory for storing a queue of sampledsignals, and may be configured to store the sampled signals in the queueand use the sampled signals stored in a queue to calculate the baselinelevel. The sensed physiological signal may be sampled during subsequentcardiac cycles to move subsequent sampled signals into the queue. Thephrenic nerve stimulation detector may dynamically adjust the baselinelevel for the physiological signal using the subsequent sampled signalsin the queue.

A system embodiment may include a cardiac pulse generator configured togenerate cardiac paces to pace the heart, a sensor configured to sense aphysiological signal for use in detecting pace-induced phrenic nervestimulation, and a phrenic nerve stimulation detector configured toanalyze the sensed physiological signal to detect the pace-inducedphrenic nerve stimulation. The system may include at least oneimplantable medical device, including the cardiac pulse generator, thesensor and the phrenic nerve detector. The system may include at leastone implantable medical device and at least one external device, wherethe implantable medical device includes the cardiac pulse generator, andthe external device includes the phrenic nerve stimulation detector.

PS Detection

Various embodiments may use PS detection techniques, includingclustering and correlation techniques to detect PS, feature-basedtechniques for detecting PS, and combinations thereof.

PS Detection Using Clustering and Correlation

Some embodiments of the present subject matter may be configured todetect the presence of PS based on the level of correlation betweenpace-gated sensor-based signals such as accelerometer signals. The term“pace-gated” indicates that the signal occurs during a window of timecorresponding to a cardiac pace such as an LV pace, for example. If acluster of beats (more than N beats) can be found with similarcorrelation, then those beats can be labeled as PS. According to someembodiments, the presence of phrenic nerve stimulation (PS) isdetermined based on the level of correlation between pace-gatedsensor-based signals, such as accelerometer signals, for example. Forexample, a correlation coefficient can be calculated for the sensedsignal and the template. By way of example and not limitation, acorrelation algorithm may use a Pearson linear correlation andcorrelation coefficients (normalized covariance function). If a clusterof beats (e.g. more than N beats) can be found with similar correlation,those beats can be labeled as PS.

The systems and devices may be configured to trigger the procedures toclassify beats using a variety of triggers. For example, the system ordevice may be commanded in-clinic or by an ambulatory patient to begin aprocedure to classify the beats. A characteristic of the PS sensorsignal may trigger the procedure. For example, if the amplitude of thesignal is larger than a predetermined value, then the system or devicemay be triggered to classify the beats. Some embodiments continuouslyclassify beats in an ambulatory setting. The beat classification may betriggered with a pace threshold test. When the procedure is triggered, atemplate library is generated based on the XL sensor signal response toa pace. As the accelerometer signal is read, it can be determinedwhether the beat matches a previous beat template in the library or not.This matching decision is based on the correlation between the currentbeat and the template. If the beat does not match any template alreadystored in the library, and there is still room to store more templates,the current beat's template is added to the library. If the beat doesmatch a template that is already stored, the tally for that template isincreased by one and the template is optionally updated with the latestbeat information. Once the tally exceeds some threshold value, thetemplate and all beats that match it (past and future) are labeled PS.In addition, the algorithm can also assess whether or not a cardiac beatcaused PS (“PS beat”) or did not cause PS (“No PS beat”) at any timewith any template.

The PS template may be a template generated by the library methoddescribed above, or, it may be provided by physician input, patientinput, a population-based pre-programmed template, or other means. Thesensor-based signal may be analyzed in a certain window around the pace,and then correlated with the PS template. If the correlation is high,then the current beat may be labeled a PS beat. If the correlation isnot high, then the current beat may be labeled a NoPS beat.

PS detectors use sensor-based signals to determine when PS occurs. Anexample of a sensor-based signal is an accelerometer signal. However,the correlation process for detecting PS may be implemented with otherPS detectors that are not accelerometer based. For example, PS sensorsignals such as impedance, muscle activity, respiration, nerve activity,and the like may be analyzed, in a certain window around the pace, andcorrelated with the PS template to determine if the pace is a PS beat ora NoPS beat.

This procedure may be implemented for ambulatory or in-clinic use. Itmay be implemented in a standalone PS detector, or in conjunction with aPS threshold test. The PS threshold test may be implemented alone as astandalone step-up and/or step-down test, or may be implemented inconjunction with a pacing threshold test (e.g. LV threshold) such thatboth the pacing threshold and the PS threshold are determined during thesame test procedure. The voltage or pulse width of the pace may beadjusted to provide a desired NoPS pace that captures the myocardialtissue.

The sensing window can be defined relative to a pace time. For example,if concerned about LV pacing causing PS, the sensing window can bedefined relative to an LV pace time or relative to an RV pace time plusan LV offset. By way of examples, and not limitation, the window may bedefined to be about 20 ms to 100 ms, or may be defined to be about 40 msto 70 ms after the LV pace. Other ranges may be used. Such windows helpavoid heart sounds or other noise in the sensed signals.

According to various embodiments, all data points, or certain datapoints, or select features of the PS sensor signal within the sensingwindow may be correlated to the template signal. A “match” can bedeclared, indicating a PS beat, if the signal or a portion of the signalwithin the sensing window exceeds a certain degree of correlation(e.g. >0.9) with the PS template in the library.

The templates in the library may be adjusted, according to someembodiments. For example, the templates can be adjusted by an average(weighted, moving, etc.) of all beats assigned to that beat type. Anamplitude or other feature of the signal for a beat may be compared tocriteria for that feature before adding a new template to the library.In addition, feature(s) of the processed signal, such as a first-orderderivative, a multiple-order derivative, or an integral, may be comparedto criteria for the feature(s).

The beat-template library may be built using a limited number oftemplates stored over time. When max storage has been reached, thetemplate with the least matches (i.e. lowest tally) is dropped from thelibrary. Each beat's correlation to the templates in the library isassessed. A defined correlation threshold can be used to identify when abeat matches a template. Every time the beat matches a template, a tallyof the beat matches for that template is increased. Once a determinednumber of matches have been found, the template and all beats whichmatch it are declared PS beats.

FIG. 12 illustrates, by way of example, an embodiment of a procedure fordeveloping a library of PS templates that may be used to discriminatebetween PS beats and NoPS beats. At 1271, a sensor-based signal, such asan accelerometer signal, is sensed within a defined window of time withrespect to a pace, referred to herein as a sensed “beat signal” toindicate that the sensed signal corresponds with a paced beat. If thesensed beat signal is the first in the library, as illustrated at 1272,then the current beat signal is stored as a template within the library,and is identified with a new beat-type label 1273. The procedure tracksthe number of beat signals that have been classified as a givenbeat-type, and uses this number to compile the templates in the library.After the current beat signal is stored as a beat-type template at 1273,a tally of the number of beats assigned to the beat type is incrementedat 1274, and the process proceeds to analyze the next paced beat (e.g.LV pace) at 1275. If the sensed beat signal is not the first in thelibrary, as illustrated at 1272, then the procedure analyzes the beatsignal to determine if the beat signal matches an existing beat-typetemplate in the library 1276. If the beat signal does not match anexisting beat-type template, then the current beat signal is stored as atemplate with a new beat-type label 1273 and the tally for thatbeat-type template is increased at 1274, assuming that a limit for thenumber of templates for the library has not been reached, as representedat 1270. If the limit for the number of templates has been reached, thena beat-type template is removed from the library at 1278 before thecurrent beat signal is stored as a beat-type template. The criteria forremoving a template may be based on the template with the lowed tally ofbeat signals that match the template, or based on the lowest amplitude,or based on a combination thereof. Other criteria may be used fordropping beat-type templates from the library. If a beat signal matchesan existing template in the library 1276, then the beat signal isidentified as a match to the beat-type template 1277 and the tally ofthe number of beat assigned to the beat type is incremented at 1278.Some embodiments may further adjust the beat-type template using thecurrent beat signal, as represented at 1279, to further fine-tune thesignal characteristics that can be used to categorize a beat signal asmatching that specific beat-type template. After the tally for thebeat-type template reaches a defined threshold 1280, then that beat-typetemplate is identified as a PS template 1281 and saved in the library asa PS template 1282. The process may stop with one PS template, or maycontinue to develop more PS templates for storage in the library for usein discriminating between PS beats and NoPS beats.

FIG. 13 illustrates, by way of example, an embodiment of a procedure forusing PS templates to discriminate between PS beats and NoPS beats. ThePS template may be determined using a procedure similar to the procedureillustrated in FIG. 12, or may be provided using other methodologies.For example, the template may be provided by a correlation library, a PSthreshold test, a morphological determination, a physician input, or apatient input. The template may be patient specific or may be apopulation-based pre-programmed template. A sensor-based signal used forPS detection is sensed within a window defined with respect to a pacedevent 1384. This sensed signal maybe referred to as a beat signal. Ifthe beat signal is determined to match a PS template 1385, then the beatsignal is identified as a PS 1386 and the system can declare thepresence of PS 1387. Some embodiments may further adjust the PS templateusing the current beat signal, as represented at 1388, to furtherfine-tune the signal characteristics that can be used to categorize abeat signal as PS. If the beat signal is determined not to match a PStemplate 1385, then the beat signal is identified as a NoPS beat 1389and the system can declare the absence of PS 1390. The determination ofwhether a beat signal matches a PS template may have a confidencefactor, such that PS is only declared if there is a high confidence thatthe beat signal is PS. A confidence factor may also be used to createmore than just a PS beat category or a NoPS category. For example, an“Unsure” category may be used.

FIG. 14 illustrates a plot of beat signals against beat-type categories,and a corresponding histogram that plots out a number of beat-typecategories and the number of beats that have been tallied in thatcategory. The figure illustrates that the present subject matter canidentify PS with a high degree of confidence.

Feature-Based PS Detection

Some embodiments of the present subject matter may be configured todetect the presence and threshold of phrenic nerve stimulation based onmorphological features of collected sensor-based signals, allowing thePS detector to automatically and accurately identify PS in the rawsignal from the PS sensor. This procedure may be used with a PSthreshold test or with a test for detecting the presence of PS. Thisprocedure may be implemented for ambulatory or in-clinic use. It may beimplemented in a standalone PS detector, or in conjunction with a PSthreshold test. The PS threshold test may be implemented alone as astandalone step-up and/or step-down test, or may be implemented inconjunction with a pacing threshold test (e.g. LV threshold) such thatboth the pacing threshold and the PS threshold are determined during thesame test procedure. The voltage or pulse width of the pace may beadjusted to provide a desired NoPS pace that captures the myocardialtissue. The systems and devices may be configured to trigger theprocedures to classify beats using a variety of triggers. For example,the system or device may be commanded in-clinic or by an ambulatorypatient to begin a procedure to classify the beats. A characteristic ofthe PS sensor signal may trigger the procedure. For example, if theamplitude of the signal is larger than a predetermined value, then thesystem or device may be triggered to classify the beats. Someembodiments continuously classify beats in an ambulatory setting. Thebeat classification may be triggered with a pacing threshold test.

Certain morphological parameters, such as peak timing and amplitude andpeak-to-peak amplitude are used to classify beats as PS beats or NoPSbeats. Features may be derived from PS sensor signals (e.g.accelerometer signals) that are observed soon after the pace. Thefeatures can be compared to certain independent weight-based criteria inorder to assign a score to each beat. Features may have a positive ornegative weight, depending on propensity of the feature for beingindicative of a PS or NoPS beat. The score for the beat is compared to apredetermined threshold to classify the beat as a PS or NoPS beat.Alternatively or in addition to scoring the features, the features canbe compared using a decision tree to provide an overall score. By usingboth a scoring algorithm and decision tree, the procedure can quicklydetermine those beats that can be quickly identified as PS beats becauseof a high amplitude, for example. The procedure can improve theclassification of and bolster confidence in the classification of loweramplitude PS beats. A confidence level on the final beat classificationmay be issued.

Examples of morphological features that can be used in the feature-basedPS detection include, but are not limited to: peak timing and amplitude,peak-to-peak amplitude, slope to and away from peak, timing andamplitude of previous and following extrema, area under the curve,signal frequency components, and significant points.

A confidence level of the decision may be determined and provided withthe PS beat or NoPS beat decision. For example, if the beat score ismuch greater than a scoring threshold, a high confidence indicator canbe provided with the decision. However, if the beat score is close tothe scoring threshold, a low confidence indicator can be provided withthe decision. A confidence level may also be determined using bothalgorithms to separately classify PS, where the classification includesa high confidence indicator if both algorithms agree and/or theclassification includes a low confidence indicator if the algorithms donot agree with each other.

FIG. 15 illustrates, by way of example, an embodiment of a procedure forusing morphological features of a sensor-based signal to discriminatebetween PS beats and NoPS beats. In the illustrated embodiment, forexample, a sensed signal may be filtered 1592. Baseline signal levels1593 may be used to identify and remove noisy beats 1594 from thediscrimination procedure. The remaining beat signals can be classifiedas PS beats or NoPS beats at 1595. For example, as illustrated at 1596the beat signal is analyzed to identify morphological parameters thatcan be used to characterize specific features of the beat signal, whichcan then be used to classify the beat signal, at 1597, using aweight-based scoring methodology, or a decision tree methodology, or acombination thereof.

FIGS. 16A-16G illustrate, by way of example, an embodiment of aprocedure for using signal peaks, as a morphological feature for asensor-based signal, to discriminate between PS beats and NoPS beats.The beat signal represents a sensed signal within a window defined inrelation to a pace. At 1601, the local extrema can be determined fordata in a first window of time 1609, using zero crossing of a firstderivative of the signal. The local extrema can be compared to identifythe maximum and minimum peaks 1602. At 1603 it may be determined if themaximum extremum occurs in a smaller window of time 1610. If the maximumextremum occurs within this smaller window of time, then the maximumextremum can be saved as a peak, as illustrated at 1604, along withsurrounding parameter information such as surrounding extremas andpeak-to-peak values. If the maximum extremum does not occur within thissmaller window of time, then it may be determined if the minimumextremum occurs within that window, as illustrated at 1605. If theminimum extremum occurs within this smaller window of time, then theminimum extremum can be saved as a peak, as illustrated at 1606, alongwith surrounding parameter information such as surrounding extremas andpeak-to-peak (P2P) values. If neither the maximum extremum nor theminimum extremum are within the smaller window of time, then the beatsignal may be analyzed to determine if it is a noisy beat 1607, in whichcase the beat would not be scored. The features of the beat signal canthen be output for scoring 1608.

FIG. 17 illustrates, by way of example, an embodiment of a procedure forscoring sensed parameters for specific morphological features. Thefigure generally illustrates that certain features can be weighted moreheavily than other features when analyzing the beat signal to determinewhether the beat signal should be classified as a PS or a NoPS beat. Theillustration uses multiple “+” symbols for some features that, in theillustrated example, may be considered higher priority features to beweighted more heavily. Examples of features that may be analyzed andscored include whether there is a prominent peak within a defined timingwindow, whether and how much greater then peak-to-peak amplitude iscompared to the baseline level, whether a previous extremum is within aspecified timing window, whether a slope between extrema is acceptableand whether a time between extrema is acceptable. Various criteria forvarious beat signal parameters may be used. Additionally, the criteriamay be weighted in a number of ways to derive an overall score for thebeat signal, which can then be used to discriminate between PS and NoPSbeats. For example, a beat can be labeled a PS beat when the scoreexceeds a threshold. The criteria may be evaluated independently, andneed not be evaluated in a particular order.

FIG. 18 illustrates, by way of example, an embodiment of a procedure forusing a decision tree for analyzing morphological features of the beatsignal to discriminate between PS beats and NoPS beats. The decisiontree presents a series of questions about the beat signal that can beanswered yes or no. The answer to a particular question may lead toanother question or to the determination for the beat signal (e.g. PSbeat or NoPS beat). Logically, the questions in the tree may be arrangedin a number of different ways to achieve the desired discrimination.Also, the analyzed parameters may vary. For example, FIG. 18 has beenorganized to analyze at the rising slope leading to the maximum peak andthe falling slope leading away from the maximum peak, and to alsoanalyze the peak-to-peak amplitudes against signal-to-noise thresholds.It is possible to analyze the peak-to-peak amplitudes againstsignal-to-noise thresholds before analyzing the slopes. Furthermore, itis possible to analyze the extrema values and timing between extremausing a number of decision points in the tree instead of or in additionto analyzing slopes. Therefore, the illustrated decision tree is but oneexample of how a decision tree can be logically arranged to discriminatebetween PS and NoPS beats.

FIG. 19 illustrates, by way of example, an embodiment of a procedure fordiscriminating PS beats using both a decision tree for analyzingmorphological features of the beat signal and scoring sensed parametersfor specific morphological features. For example, a first question inthe decision tree may be crafted to identify the beat signals that areclearly PS beats 1909. A PS beat may be clearly identifiable based on asignal-to-noise ratio or based on other criteria that can be quicklydetermined with relatively little processing. If the beat signal cannotbe identified as clearly a PS beat, then it can be determined if thebeat signal is likely a PS beat 1910. This also may be determined basedon a signal-to-noise ratio or on other criteria that can be quicklydetermined with relatively little processing. If the beat signal isdetermined to likely be a PS beat, then the PS beat can be confirmedwith another decision tree question 1911 (e.g. Is the next slope greaterthan a threshold?). If the PS beat cannot be confirmed at 1911, then themorphological feature(s) of the beat signal can be scored at 1913. Ifthe beat signal cannot be determined to likely be a PS beat at 1910,then the beat signal is a non-obvious beat signal 1912, and themorphological feature(s) of the beat signal can be scored at 1913. Thescoring may use weighted scoring of multiple morphological features,such as scoring based on slope 1914, based on distances between extrema1915, and/or based on other morphological features of the beat signal.

Scoring—Correlation Combination

Some embodiments of the present subject matter may be configured todetect the presence and threshold of phrenic nerve stimulation based ona combination approach using both a correlation between the PS sensorsignal and a template, and morphological feature-based score of the PSsensor signal which may use a feature score and/or decision tree. Whentriggered, a template library may be generated based on the beat signal.As the beat signal is read, it can be determined if the beat signalmatches a previous beat-type template in the library. This matchingdecision is based on the correlation between the current beat and thebeat-template. If the beat does not match any template already stored inthe library, and there is still room to store more templates, thecurrent beat's template is scored with the morphological featurealgorithm. This score determines whether to annotate the template as PSor NoPS. The annotated template will then be added to the library. Ifthe beat does match a template that is already stored, the annotation ofthat template will determine if the current beat is a PS beat or NoPSbeat.

In some embodiments, the algorithm may also assess whether or not a beatis a PS beat or a NoPS beat, at any time with any template. The templatemay be a template generated by the library method discussed above, or,it could be from some other method (physician input, patient input, apopulation-based pre-programmed template, etc.). Some embodiments maygenerate templates from the beat signal in parallel with scoringfeatures of the beat signal. If the score is high enough, the beat maybe quickly labeled as a PS beat. If the score is too low, the beat maybe labeled a NoPS beat. If the score is somewhere in the middle however,the correlation of the beat with the stored PS template may be assessedto determine that the beat signal is a PS beat if it correlates with thePS template, or determine that the beat signal is a NoPS beat if it doesnot correlate with the PS template. Thus, with the use of the scoringmethod to quickly categorize the beat signal, fewer beat signals arecorrelated to a template which reduces the overall processing todiscriminate between PS beats and NoPS beats.

Many different types of PS and No PS templates can be generated andstored. According to various embodiments, template libraries may becreated to only store PS beat templates, or to only store NoPS beattemplates, or to store both PS beat templates and NoPS beat templates.

The systems and devices may be configured to trigger the procedures toclassify beats using a variety of triggers. For example, the system ordevice may be commanded in-clinic or by an ambulatory patient to begin aprocedure to classify the beats. A characteristic of the PS sensorsignal may trigger the procedure. For example, if the amplitude of thesignal is larger than a predetermined value, then the system or devicemay be triggered to classify the beats. Some embodiments continuouslyclassify beats in an ambulatory setting. The beat classification may betriggered with a pacing threshold test. Score here, as in advancedtemplate generation, is a general term to refer to the output of themorphological feature-based algorithm. The score may be the score resultfrom the scoring version, or could be a level of confidence associatedwith the number of tree branches accessed. By including the correlationstep with the result of the morphological feature-based algorithm, thefeature-based algorithm can be more sensitive to PS beats without theworry of false-positive detections or false-negatives.

FIG. 20 illustrates, by way of example, an embodiment of a procedure fordiscriminating PS beats that uses correlation to create templates in alibrary and to score the beat signals to quickly identify the beat-typetemplates that can be labeled as a PS template. FIG. 20 has similaritiesto FIG. 12, which was described in detail above and need not be repeatedhere. However, differences between FIG. 20 and FIG. 12 are illustratedat 2016, 2017, and 2018. If a beat signal does not match an existingbeat-type template, either because it is a new beat signal for a librarywithout beat-type templates or because the beat signal does not matchthe beat-type templates stored in the library, the morphologicalfeature(s) of the beat signal can be scored at 2016. The score may be aweighted score of the features. The score can be compared to a definedscore threshold at 2017. If the score is high enough, for example, thebeat signal can quickly be classified as a PS template at 2018 with ahigh degree of confidence, and beat signal can be classified as anddeclared a PS beat.

FIG. 21 illustrates, by way of example, an embodiment of a procedure fordiscriminating PS beats that scores morphological features of the beatsignals to quickly identify some beat signals as PS beats or NoPS beats,and that correlates the remainder of the beat signals to a PS templateto discriminate between PS beats and NoPS beats. In the illustratedembodiment, once a beat classification procedure has been triggered2119, the procedure may determine if a PS template is stored in thesystem 2120. If it is not stored in the system, the PS template isobtained 2121. The PS template may be created in some embodiments, ormay be input by a patient or physician. The PS template may be patientspecific or based on a population of patients. If the PS template isalready stored, the PS template is retrieved 2122 for a correlationprocedure. In parallel, the beat signal in the window of time after thepace is analyzed 2123, and the morphological features of the beat signalare scored 2124. The score can be compared to a first value 2125 todetermine if the beat signal is clearly a PS beat requiring no furtherverification 2126, and can be compared to a second value 2127 todetermine if the beat signal is clearly a NoPS beat requiring no furtherverification 2128. If the scoring algorithm is unable to identify thebeat signal as clearly either a PS beat or a NoPS beat, then the beatsignal can be correlated with the PS template 2129 to determine if thebeat signal is a PS beat 2130 or a NoPS beat 2131.

In an example of a method for detecting PS beats, the method may includepacing a heart with cardiac paces, sensing a physiological signal foruse in detecting PS beats where sensing the physiological signalincludes sensing beat signals from a window of time defined based oncardiac pace times, building a library of beat-type templates includingstoring beat signal data for the sensed beat signals in beat-typetemplates, and using the PS template to detect PS beats. Storing beatsignal data may include determining if the beat signal data for acurrently-analyzed beat signal matches an existing beat-type template inthe library, and creating a new beat-type template if there is no matchor increasing a tally for the beat-type template if there is a match,and declaring that one of the beat-type templates to be a PS templatewhen the tally for one of the beat-type templates reaches a definedthreshold.

In an example of a method for detecting PS beats, the method may includepacing a heart with cardiac paces, sensing a physiological signal foruse in detecting PS beats where sensing the physiological signalincludes sensing beat signals from a window of time defined based oncardiac pace times, identifying morphological features for a sensed beatsignal, and using the identified morphological features to determine ifthe sensed beat signal is a PS beat. Using the identified morphologicalfeatures to determine if the sensed beat signal is a PS beat may includeusing weight-based scoring of the identified morphological features toanalyze the identified morphological features. Using the identifiedmorphological features to determine if the sensed beat signal is a PSbeat may include using a decision tree to analyze the identifiedmorphological features.

In an example of a method for detecting PS beats, the method may includepacing a heart with cardiac paces, sensing a physiological signal foruse in detecting PS beats where sensing the physiological signalincludes sensing beat signals from a window of time defined based oncardiac pace times, building a library of beat-type templates includingstoring beat signal data for the sensed beat signals in beat-typetemplates. Storing beat signal data may include determining if beatsignal data for a currently-analyzed beat signal matches an existingbeat-type template in the library, scoring the beat signal data for thesensed beat signals and creating a score-generated PS template from thebeat signal data if there is no match to an existing beat-type templateand if the score favorably compares to a defined threshold for thescore, creating a new beat-type template if there is no match and thescore does not favorably compare to the defined threshold for the score,and increasing a tally for the beat-type template if there is a matchand declaring the beat type template to be a clustering-generated PStemplate when the tally reaches a defined tally threshold. The methodmay further include detecting PS beats using the score-generated PStemplate or the clustering-generated PS template.

In an example of a method for detecting PS beats, the method may includepacing a heart with cardiac paces, sensing a physiological signal foruse in detecting PS beats where sensing the physiological signalincludes sensing beat signals from a window of time defined based oncardiac pace times, scoring morphological features of the sensed beatsignals, using the score to identify those sensed beat signals that canbe declared PS beats with a high degree of confidence and those sensedbeat signals that can be declared NoPS beats with a high degree ofconfidence, and correlating sensed beats that cannot be declared, with ahigh degree of confidence, as either PS beats or NoPS beats to a PStemplate, and declaring the sensed beats that are correlated with the PStemplate to be PS beats.

In an example, a system includes a cardiac pulse generator configured togenerate cardiac paces to pace the heart, a sensor configured to sense aphysiological signal for use in detecting pace-induced phrenic nervestimulation where the pace-induced phrenic nerve stimulation is phrenicnerve stimulation induced by electrical cardiac pace signals, and aphrenic nerve stimulation detector configured to analyze the sensedphysiological signal to detect PS beats where the PS beats are cardiacpaces that induce phrenic nerve stimulation. The phrenic nervestimulation detector may be configured to correlate signal data forsensed beat signals to a PS template to detect PS beats, or may beconfigured to analyze morphological features of sensed beat signals todetect PS beats, or may be configured to detect PS beats using acombination that both correlates signal data for sensed beat signals toa PS template and analyzes morphological features of sensed beatsignals.

PS Stimulation Threshold Determination

Some embodiments of the present subject matter may be configured todetect the presence and threshold of phrenic nerve stimulation (PS)using a step-up test or step-down test or a combination of the step-upand step-down tests. The PS threshold may be determined alone or inconjunction with a pace capture threshold test (e.g. an LV thresholdtest). An LV threshold test often is a step-down test that initiallyuses a high energy pace to confirm capture of the myocardium and thatsteps down the pacing energy to determine the lowest pacing energy levelthat still paces the heart. The PS threshold tests may either adjust thepacing amplitude or pulse width to determine the PS threshold. A pacingoutput level refers to a pacing energy level that may be based on anamplitude of the paces and/or a pulse width of the paces. In addition,the PS threshold may be determined using a combination of step-up andstep-down tests. The step sizes may be predefined, or may be dynamicallyadjusted based on the observed results during the test.

In a step-up test, the pacing voltage may be increased by predefinedintervals until PS is observed over several beats or with a highresponse amplitude. If there is not high confidence that PS has beendetected, a PS confirmation step may be conducted. The pacing output maybe increased for several cardiac cycles, increasing the likelihood ofstimulating the phrenic nerve, to determine if the same PScharacteristics are observed. Alternatively or additionally, the pacingoutput may be decreased to determine the characteristics of NoPS beatsfor comparison.

In a step-down test, the pacing voltage may be decreased bypre-determined intervals until PS is no longer observed over severalbeats. Alternatively, the pacing output decrease may be adaptivelyadjusted based on the amplitude of PS response. For instance, a largerpacing output decrease could be employed when a large PS amplitude andhigh PS frequency are observed.

According to some embodiments, the pacing parameters are adaptivelyadjusted during a test based on the patient's PS response to quickly andaccurately measure PS threshold. For example, some embodiments adjustpacing amplitude output, or pulse width output, or the number of pacesat a level, or a combination thereof. Thus, the test can be implementedto determine an appropriate characteristic of a myocardial pace (e.g. anappropriate amplitude and/or pulse width) that avoids PS.

The pacing output can be adaptively adjusted based on the PS response. Alarger pacing output drop could be used when a higher PS amplitude tobaseline ratio or higher frequency is observed. When PS amplitude frommultiple steps are observed, a linear or polynomial or other functionsmay be fitted over the PS response to adjust the pacing outputsubsequently. A step-up process may be initiated when PS responsedisappears after the output adjustment.

FIG. 22 illustrates, by way of example, an embodiment of a step-upprocedure for determining a PS threshold. The illustrated procedure maybe used as a standalone process for determining PS threshold or inconjunction with an LV step-up threshold test. When used as a standalonetest, the procedure may use coarser steps. When used with an LV step-upthreshold test, finer step intervals are used, and beat signals frommultiple consecutive levels can be used.

The illustrated step-up procedure is initiated with a relatively lowpacing output 2232, and a defined number of paces are delivered at thepacing level 2233. The beat signals are analyzed to determine if PSbeats were observed at the pacing level 2234. If no PS beats wereobserved, the pacing output is increased to a higher pacing output level2235. If PS beats were observed, then the observed PS beats orcharacteristics thereof may be compared to one or more thresholds at2236. For example, the number of PS beats that were observed at thelevel may be compared to a threshold number. In another example, a ratioof the amplitude of the observed PS beat(s) to the baseline level may becompared to a threshold. The pacing level may be declared to be the PSthreshold 2237 based on the comparison, or further PS confirmation maybe performed 2238. The threshold or thresholds may be set based onphysician preference. Furthermore, the procedure may differ depending onwhether the test is performed in a clinical setting or in an ambulatorysetting. For example, clinical settings may not require the PSconfirmation.

FIG. 23 illustrates, by way of example, an embodiment of a procedure forconfirming a PS threshold by increasing the pacing output level. If somebeat signals appear to be PS beats for a pacing level from FIG. 22, thenthe illustrated procedure delivers additional paces at the same pacinglevel 2339. If PS beats were observed, then the observed PS beats orcharacteristics thereof may be compared to one or more thresholds at2340. For example, the number of PS beats that were observed at thepacing output level may be compared to another threshold numberdifferent from the threshold used at 2236 in FIG. 22. In anotherexample, a ratio of the amplitude of the observed PS beat(s) to thebaseline level may be compared to another threshold different from thethreshold used at 2236 in FIG. 22. If the comparison is favorable, thenthe pacing level can be declared to be the PS threshold and the test canbe stopped 2341. Otherwise, the procedure increases pacing output leveland delivers an additional number of paces 2342. The increase in thepacing output may depend on the frequency and/or the amplitude of theobserved PS beats. For example, the increase interval may be less forlarger PS beat amplitudes or if more PS beats were observed as thecurrent pacing output level is close to the PS threshold. Coarser stepsmay be used. Some embodiments may use fixed intervals to adjust thepacing output levels. If PS beats are not observed 2343, then thestep-up test continues at 2344 in the illustrated embodiment. If PSbeats are observed 2343, then the observed PS beats or characteristicsthereof may be compared to one or more thresholds at 2345. For example,the number of PS beats that were observed at the level may be comparedto another threshold number different from the thresholds used at 2236in FIG. 22 or 2340. In another example, a ratio of the amplitude of theobserved PS beat(s) to the baseline level may be compared to anotherthreshold different from the thresholds used at 2236 in FIG. 22 or 2340.If the comparison is not favorable at 2345, the pacing output level canbe increased and the confirmation can be repeated 2346. If thecomparison is favorable at 2345, then some embodiments may furthercompare the signal characteristics between the confirmation level andthe level where PS beats were first observed for similarities 2347, anddeclare the previous level as the PS threshold 2348A if there aresimilarities. If there are not similarities found in the comparisonperformed at 2347, the output level can be stepped-down to a levelbetween the level at which the PS beats were first observed and theconfirmation level to further refine the PS threshold, and theconfirmation can be repeated 2348B.

FIG. 24 illustrates, by way of example, an embodiment of a procedure forconfirming a PS threshold by reducing the pacing output level. If somebeat signals appear to be PS beats for a pacing level from FIG. 22, thenthe illustrated procedure delivers additional paces at the same pacinglevel 2449. If PS beats were observed, then the observed PS beats orcharacteristics thereof may be compared to one or more thresholds at2450. For example, the number of PS beats that were observed at thelevel may be compared to a second threshold number different from thethreshold used at 2236 in FIG. 22. In another example, a ratio of theamplitude of the observed PS beat(s) to the baseline level may becompared to a second threshold different from the threshold used at 2236in FIG. 22. If the comparison is favorable, then the pacing level can bedeclared to be the PS threshold and the test can be stopped 2451. If thecomparison is not favorable, then a defined number of “empty” paces aredelivered at 2452 in an attempt to see if similar PS beat signatureswere observed. Empty paces can be delivered by reducing an LV pacingoutput to a very low value, such as 0.1 V, or by delivering RV pace andanalyzing the signals based on the RV-LV offset. If similar PS beatcharacteristics are not observed at 2453, then the level can be declaredto be the PS threshold and the test can be stopped at 2451. The “empty”pace should still provide the same cardiac components, which allow for ameaningful comparison. The pacing level for an empty pace may beadjusted to a level that has LV capture but does not have PS. If similarPS beat characteristics are observed at 2453, then the step-up test inFIG. 22 continues as indicated at 2454.

FIG. 25 illustrates, by way of example, an embodiment of a step-downprocedure for determining a PS threshold. The illustrated procedure maybe used as a standalone process for determining PS threshold or inconjunction with an LV step-up threshold test. When used as a standalonetest, the procedure may use coarser steps. When used with an LV step-upthreshold test, finer step intervals are used, and beat signals frommultiple consecutive levels can be used.

A procedure is initiated with a relatively high pacing output 2555, anda defined number of paces are delivered at the pacing level 2556. Thebeat signals are analyzed to determine if PS beats were observed at thepacing level 2557. The analysis of the beat signals may include aprocedure disclosed. If no PS beats were observed, then the test can bestopped or a step-up test may be initiated from the current pacingoutput 2558. If PS beats were observed, then the observed PS beats orcharacteristics thereof may be compared to one or more thresholds at2559. For example, the number of PS beats that were observed at thelevel may be compared to a threshold number. In another example, a ratioof the amplitude of the observed PS beat(s) to the baseline level may becompared to a threshold. The pacing level may be declared to be the PSthreshold 2560 based on the comparison. If the comparison is notfavorable, the pacing output can be decreased at 2561 and the test cancontinue at 2556. The pacing output decrease may be performed adaptivelybased on the PS beats using, by way of example, the amplitude of the PSbeats, the ratio of the amplitude of the PS beats to the baseline level,the frequency of PS beats, or various combinations thereof. Thethreshold may be set based on physician preference. Furthermore, theprocedure may differ depending on whether the test is performed in aclinical setting or in an ambulatory setting.

In an example of a method, the method includes testing for the phrenicnerve stimulation (PS) threshold. If PS beats are detected at the pacingoutput level, the detected PS beats may be analyzed using criteria todetermine if the pacing output level can be declared to be the PSthreshold. If the pacing output level cannot be declared to be the PSthreshold based on the analysis of the PS beat at the pacing outputlevel, a PS beat confirmation procedure may be performed. The PS beatconfirmation procedure may include delivering additional cardiac pacesat the pacing output level to generate additional PS beats, andanalyzing the detected PS beats using other criteria to determine if thepacing output level can be confirmed as the PS threshold.

In an example, a system includes a cardiac pulse generator configured togenerate cardiac paces to pace the heart, a sensor configured to sense aphysiological signal for use in detecting pace-induced phrenic nervestimulation, a phrenic nerve stimulation detector configured to analyzethe sensed physiological signal to detect PS beats, and a controllerconfigured to test for phrenic nerve stimulation (PS) threshold. Thecontroller may be configured to control the cardiac pulse generator todeliver cardiac paces at a pacing output level, use the phrenic nervestimulation detector to detect if the pacing output level causes PSbeats, analyze the detected PS beats if PS beats are detected at thepacing output level, and perform a PS beat confirmation procedure if thepacing output level cannot be declared to be the PS threshold based onthe analysis of the PS beat at the pacing output level. To analyze thedetected PS beats, the controller may use criteria to determine if thepacing output level can be declared to be the PS threshold. The PS beatconfirmation procedure may include delivering additional cardiac pacesat the pacing output level to generate additional PS beats, andanalyzing the detected PS beats using other criteria to determine if thepacing output level can be confirmed as the PS threshold. The system mayinclude at least one implantable medical device that includes thecardiac pulse generator, the sensor, the phrenic nerve stimulationdetector and the controller. The system may include at least oneimplantable medical device and at least one external device, where theimplantable medical device(s) include the cardiac pulse generator, andthe external device(s) including the phrenic nerve stimulation detector.One of ordinary skill in the art will understand that, the modules andother circuitry shown and described herein can be implemented usingsoftware, hardware, firmware and combinations thereof.

The methods illustrated in this disclosure are not intended to beexclusive of other methods within the scope of the present subjectmatter. Those of ordinary skill in the art will understand, upon readingand comprehending this disclosure, other methods within the scope of thepresent subject matter. The above-identified embodiments, and portionsof the illustrated embodiments, are not necessarily mutually exclusive.These embodiments, or portions thereof, can be combined. In variousembodiments, the methods are implemented using a sequence ofinstructions which, when executed by one or more processors, cause theprocessor(s) to perform the respective method. In various embodiments,the methods are implemented as a set of instructions contained on acomputer-accessible medium such as a magnetic medium, an electronicmedium, or an optical medium.

The above detailed description is intended to be illustrative, and notrestrictive. Other embodiments will be apparent to those of skill in theart upon reading and understanding the above description. The scope ofthe invention should, therefore, be determined with reference to theappended claims, along with the full scope of equivalents to which suchclaims are entitled.

What is claimed is:
 1. A method, comprising: testing for phrenic nervestimulation (PS) threshold, including: pacing a heart with cardiac pacesat a pacing output level; sensing a physiological signal for use indetecting PS beats, wherein the PS beats are cardiac paces that inducephrenic nerve stimulation; and monitoring for PS beats in the sensedphysiological signal to detect if the pacing output level causes PSbeats; if PS beats are detected at the pacing output level, analyzingthe detected PS beats using criteria to determine if the pacing outputlevel can be declared to be the PS threshold; and if the pacing outputlevel cannot be declared to be the PS threshold based on the analysis ofthe PS beat at the pacing output level, performing a PS beatconfirmation procedure including: delivering additional cardiac paces atthe pacing output level to generate additional PS beats; and analyzingthe detected PS beats using other criteria to determine if the pacingoutput level can be confirmed as the PS threshold.
 2. The method ofclaim 1, wherein testing for phrenic nerve stimulation thresholdincludes performing a step-up test, the step-up test including if PSbeats are not detected at the pacing output level, increasing the pacingoutput level and retesting for the phrenic nerve stimulation thresholdat the increased pacing output level.
 3. The method of claim 2, whereinin performing the step-up test, analyzing the detected PS beats usingcriteria to determine if the pacing output level can be declared to bethe PS threshold includes determining if a number of detected PS beatsis greater than a defined number to declare the pacing threshold to bethe PS threshold.
 4. The method of claim 2, wherein in performing thestep-up test, analyzing the detected PS beats using criteria todetermine if the pacing output level can be declared to be the PSthreshold includes determining if a ratio of an amplitude of the PSbeats to a baseline output level exceed a defined number to declare thepacing threshold to be the PS threshold.
 5. The method of claim 2,wherein in performing the step-up test, analyzing the detected PS beatsusing criteria to determine if the pacing output level can be declaredto be the PS threshold includes: determining if a number of detected PSbeats is greater than a defined number to declare the pacing thresholdto be the PS threshold; and determining if a ratio of an amplitude ofthe PS beats to a baseline output level exceed a defined number todeclare the pacing threshold to be the PS threshold.
 6. The method ofclaim 2, wherein increasing the paced output level includes dynamicallyadjusting an interval for increasing the pacing output level based onthe analysis of the PS beats.
 7. The method of claim 2, wherein if thepacing output level cannot be declared to be the PS threshold based onthe analysis of the detected PS beats using the other criteria,performing a second PS beat confirmation procedure including: increasingthe pacing output level, and delivering additional cardiac paces at theincreased pacing output level to generate additional PS beats; andanalyzing the detected PS beats at the increased pacing output levelusing criteria to determine if the pacing output level can be confirmedas the PS threshold.
 8. The method of claim 2, wherein if the pacingoutput level cannot be declared to be the PS threshold based on theanalysis of the detected PS beats using the other criteria, performing asecond PS beat confirmation procedure including: delivering additionalcardiac paces at the pacing output level to generate additional PSbeats; and analyzing the detected PS beats using different criteria todetermine if the pacing output level can be confirmed as the PSthreshold.
 9. The method of claim 8, further comprising: decreasing thepacing output level if the pacing output level cannot be confirmed asthe PS threshold using the different criteria; delivering additionalcardiac paces at the decreased pacing output level to generateadditional PS beats; and comparing the detected PS beats at thedecreased pacing output level for characteristics similar to thedetected PS beats previously analyzed using the different criteria. 10.The method of claim 1, wherein testing for phrenic nerve stimulationthreshold includes performing a step-down test, the step-down testincluding decreasing the pacing output level if the detected PS beatsindicate that the pacing output level is higher than the PS threshold.11. The method of claim 10, wherein in performing the step-down test,analyzing the detected PS beats using criteria to determine if thepacing output level can be declared to be the PS threshold includesdetermining if a number of detected PS beats is less than a definednumber to declare the pacing threshold to be the PS threshold.
 12. Themethod of claim 10, wherein in performing the step-down test, analyzingthe detected PS beats using criteria to determine if the pacing outputlevel can be declared to be the PS threshold includes determining if aratio of an amplitude of the PS beats to a baseline output level is lessthan a defined number to declare the pacing threshold to be the PSthreshold.
 13. The method of claim 10, wherein in performing thestep-down test, analyzing the detected PS beats using criteria todetermine if the pacing output level can be declared to be the PSthreshold includes: determining if a number of detected PS beats is lessthan a defined number to declare the pacing threshold to be the PSthreshold; and determining if a ratio of an amplitude of the PS beats toa baseline output level is less than a defined number to declare thepacing threshold to be the PS threshold.
 14. The method of claim 1,wherein the method is performed by using an implantable medical devicein an ambulatory patient away from a clinical setting.
 15. The method ofclaim 1, wherein the method is performed in a clinical setting.
 16. Themethod of claim 1, wherein if the pacing output level cannot be declaredto be the PS threshold based on the analysis of the detected PS beatsusing the other criteria, changing the pacing output level, deliveringadditional cardiac paces at the changed pacing output level, andanalyzing the sensed physiological signal at the changed pacing outputlevel using criteria to determine if the pacing output level can beconfirmed as the PS threshold.
 17. The method of claim 16, whereinanalyzing the sensed physiological signal at the changed pacing outputlevel includes comparing: a number of detected PS beats to a definednumber, or a ratio of an amplitude of detected PS beats to a baselineoutput to a defined ratio.
 18. A system, comprising: a cardiac pulsegenerator configured to generate cardiac paces to pace the heart; asensor configured to sense a physiological signal for use in detectingpace-induced phrenic nerve stimulation, wherein the pace-induced phrenicnerve stimulation is phrenic nerve stimulation induced by electricalcardiac pace signals; a phrenic nerve stimulation detector configured toanalyze the sensed physiological signal to detect PS beats, wherein thePS beats are cardiac paces that induce phrenic nerve stimulation; acontroller configured to test for phrenic nerve stimulation (PS)threshold, wherein the controller is configured to: control the cardiacpulse generator to deliver cardiac paces at a pacing output level; usethe phrenic nerve stimulation detector to detect if the pacing outputlevel causes PS beats; analyze the detected PS beats, if PS beats aredetected at the pacing output level, using criteria to determine if thepacing output level can be declared to be the PS threshold; and performa PS beat confirmation procedure, if the pacing output level cannot bedeclared to be the PS threshold based on the analysis of the PS beat atthe pacing output level, that includes delivering additional cardiacpaces at the pacing output level to generate additional PS beats, andanalyzing the detected PS beats using other criteria to determine if thepacing output level can be confirmed as the PS threshold.
 19. The systemof claim 18, wherein: the controller is configured to perform a step-uptest, the step-up test including increasing the pacing output level andretesting for the phrenic nerve stimulation threshold at the increasedpacing output level if PS beats are not detected at the pacing outputlevel; or the controller is configured to perform a step-down test, thestep-down including decreasing the pacing output level if the detectedPS beats indicate that the pacing output level is higher than the PSthreshold.
 20. A method, comprising: testing for phrenic nervestimulation (PS) threshold, including: pacing a heart with cardiac pacesat a pacing output level: sensing a physiological signal tier use indetecting PS beats, wherein the PS beats are cardiac paces that inducephrenic nerve stimulation; and monitoring for PS beats in the sensedphysiological signal to detect if the pacing output level causes PSbeats; if PS beats are detected at the pacing output level, analyzingthe detected PS beats using criteria to determine if the pacing outputlevel can be declared to be the PS threshold; and if the pacing outputlevel cannot be declared to be the PS threshold based on the analysis ofthe PS beat at the pacing output level, performing a PS beatconfirmation procedure including: changing the pacing output level;delivering additional cardiac paces at the changed pacing output level;and analyzing the sensed physiological signal at the changed pacingoutput level using criteria to determine if the pacing output level canbe confirmed as the PS threshold.